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Hypersensitivity: Allergy, Autoimmunity, and Alloimmunity
- Hypersensitivity is an inappropriate immune response misdirected against the host’s own tissues (autoimmunity) or directed against beneficial foreign tissues, such as transfusions or transplants (alloimmunity); or it can be exaggerated responses against environmental antigens (allergy).
- Mechanisms of hypersensitivity are classified as type I (IgE-mediated) reactions, type II (tissue-specific) reactions, type III (immune-complex-mediated) reactions, and type IV (cell-mediated) reactions.
- Hypersensitivity reactions can be immediate (developing within seconds or hours) or delayed (developing within hours or days).
- Anaphylaxis, the most rapid immediate hypersensitivity reaction, is an explosive reaction that occurs within minutes of re-exposure to the antigen and can lead to cardiovascular shock.
- Allergens are antigens that cause allergic responses.
- Type I (IgE-mediated) reactions are occur after antigen reacts with IgE on mast cells, leading to mast cell degranulation and the release of histamine and other inflammatory substances.
- Type II (tissue-specific) reactions are caused by four possible mechanisms: complement-mediated lysis, opsonization and phagocytosis, antibody-dependent cell-mediated cytotoxicity, and modulation of cellular function.
- Type III (immune complex-mediated) reactions are caused by the formation of immune complexes that are deposited in target tissues, where they activate the complement cascade, generating chemotactic fragments that attract neutrophils into the inflammatory site.
- Immune-complex disease can be a systemic reaction, such as serum sickness (e.g., Raynaud phenomenon), or localized, such as the Arthus reaction.
- Type IV (cell-mediated) reactions are caused by specifically sensitized T cells, which either kill target cells directly or release lymphokines that activate other cells, such as macrophages.
- Allergies can be mediated by any of the four mechanisms of hypersensitivity.
- Clinical manifestations of allergic reactions are usually confined to the areas of initial intake or contact with the allergen. Ingested allergens induce gastrointestinal symptoms, airborne allergens induce respiratory or skin manifestations, and contact allergens induce allergic responses at the site of contact.
- Atopic individuals are genetically predisposed to the development of allergies.
- Alloimmunity is the immune system’s reaction against antigens on the tissues of other members of the same species.
- Alloimmune disorders include transient neonatal disease, in which the maternal immune system becomes sensitized against antigens expressed by the fetus and transplant rejection and transfusion reactions, in which the immune system of the recipient of an organ transplant or blood transfusion reacts against foreign antigens on the donor’s cells.
- Bacteria injure cells by producing exotoxins or endotoxins, Exotoxins are enzymes that can damage the plasma membranes of host cells or can inactivate enzymes critical to protein synthesis, and endotoxins activate the inflammatory response and produce fever.
- Septicemia is the proliferation of bacteria in the blood. Endotoxins released by blood-borne bacteria cause the release of vasoactive enzymes that increase the permeability of blood vessels. Leakage from vessels causes hypotension that can result in septic shock.
- Viruses enter host cells and use the metabolic processes of host cells to proliferate.
- Viruses that have invaded host cells may decrease protein synthesis, disrupt lysosomal membranes, form inclusion bodies where synthesis of viral nucleic acids is occurring, fuse with host cells to produce giant cells, alter antigenic properties of the host cell, and transform host cells into cancerous cells.
- Diseases caused by fungi are called mycoses, and they occur in two forms: yeasts (spheres) and molds (filaments or hyphae).
- Dermatophytes are fungi that infect skin, hair, and nails with diseases such as ringworm and athlete’s foot.
- Fungi release toxins and enzymes that are damaging to tissue.
Deficiencies in Immunity
- Immunodeficiency is the failure of mechanisms of self-defense to function in their normal capacity.
- Immunodeficiencies are either congenital (primary) or acquired (secondary). Congenital immunodeficiencies are caused by genetic defects that disrupt lymphocyte development, whereas acquired immunodeficiencies are secondary to disease or other physiologic alterations.
- The clinical hallmark of immunodeficiency is a propensity to unusual or recurrent severe infections. They type of infection usually reflects the immune system defect.
- The most common infections in individuals with defects of cell-mediated immune response are fungal and viral, whereas infections in individuals with defects of the humoral immune response or complement function are primarily bacterial.
- Severe combined immunodeficiency (SCID) is a total lack of T cell function and a severe (either partial or total) lack of B cell function.
- DiGeorge syndrome (congenital thymic aplasia or hypoplasia) is characterized by complete or partial lack of the thymus (resulting in depressed T cell immunity), the parathyroid glands (resulting in hypocalcemia), and cardiac anomalies.
- Defects in B cell function are diverse, ranging from a complete lack of the human bursal equivalent, the lymphoid organs required for B cell maturation (as in Bruton agammgolunlinemia), to deficiencies in a single class of immunoglobulins (e.g., selective IgA deficiency).
- Acquired immunodeficiencies are caused by super-imposed conditions, such as malnutrition, medical therapies, physical or psychologic trauma, or infections.
- AIDS is an acquired dysfunction of the immune system caused by a retrovirus (HIV) that infects and destroys CD4+ lymphocytes (helper T cells).
- Immunodeficiency syndromes usually are treated by replacement therapy. Deficient antibody production is treated by replacement of missing immunoglobulins with commercial gamma-globulin preparations. Lymphocyte deficiencies are treated with the replacement of host lymphocytes with transplants of bone marrow, fetal liver, or fetal thymus from a donor.